The effect of cytokines on parathyroid hormone-related protein (PTH-rP) production in human amnion cells

In the present study, the effects of various cytokines on parathyroid hormo ne-related protein (PTH-rP) production and PTH-rP mRNA expression in human amnion cells were studied. Immunoreactive (ir) PTH-rP was measured by immun oradiometric assay and the expression of PTH-rP mRNA was determined by Nort hern blot analysis. The addition of interleukin-1 beta (IL-1 beta, 10 ng/ml ) and IL-6 (10 ng/ml) in culture medium for 24 hours resulted in a signific ant increase in ir-PTH-rP levels by 1.5 and 1.6 fold, respectively. The eff ects of these agents were dose dependent. In contrast, IL-2 (10 ng/ml) and IL-8 (10 ng/ml) showed no effect on the production of ir-PTH-rP from amnion cells. Treatment with IL-1 beta or IL-6 for 6 hours increased the expressi on of PTH-rP mRNA in amnion cells. The stimulatory effect of IL-1 beta was reduced by IL-1 receptor antagonist (IL-1Ra) in a dose dependent manner. Bo th tetradecanoyl phorbol acetate (TPA), and forskolin increased PTH-rP mRNA levels and the PTH-rP production in amnion cells, and the effect of TPA wa s much greater than that of forskolin. The findings of the present study su ggest of the participation of inflammatory cytokines for the regulation of PTH-rP production in human amnion cells.